Minimally-invasive heart valve with cusp positioners

ABSTRACT

A prosthetic heart valve having an internal support frame with a continuous, undulating leaflet frame defined therein. The leaflet frame has three cusp regions positioned at an inflow end intermediate three commissure regions positioned at an outflow end thereof. The leaflet frame may be cloth covered and flexible leaflets attached thereto form occluding surfaces of the valve. The support frame further includes three cusp positioners rigidly fixed with respect to the leaflet frame and located at the outflow end of the support frame intermediate each pair of adjacent commissure regions. The valve is desirably compressible so as to be delivered in a minimally invasive manner through a catheter to the site of implantation. Upon expulsion from catheter, the valve expands into contact with the surrounding native valve annulus and is anchored in place without the use of sutures. In the aortic valve position, the cusp positioners angle outward into contact with the sinus cavities, and compress the native leaflets if they are not excised, or the aortic wall if they are. The support frame may be formed from a flat sheet of Nitinol that is bent into a three-dimensional configuration and heat set. A holder having spring-like arms connected to inflow projections of the valve may be used to deliver, reposition and re-collapse the valve, if necessary.

FIELD OF THE INVENTION

The present invention relates generally to medical implants, and moreparticularly to minimally-invasive or collapsible/expandable heartvalves and methods of delivering and implanting such valves.

BACKGROUND OF THE INVENTION

Prosthetic heart valves are used to replace damaged or diseased heartvalves. In vertebrate animals, the heart is a hollow muscular organhaving four pumping chambers: the left and right atria and the left andright ventricles, each provided with its own one-way valve. The naturalheart valves are identified as the aortic, mitral (or bicuspid),tricuspid and pulmonary valves. Prosthetic heart valves can be used toreplace any of these naturally occurring valves, although repair orreplacement of the aortic or mitral valves is most common because theyreside in the left side of the heart where pressures are the greatest.

Where replacement of a heart valve is indicated, the dysfunctional valveis typically cut out and replaced with either a mechanical valve, or atissue or bioprosthetic-type valve. Bioprosthetic-type valves are oftenpreferred over mechanical valves because they typically do not requirelong-term treatment with anticoagulants. The most commonbioprosthetic-type valves are constructed with whole porcine (pig)valves, or with separate leaflets cut from bovine (cow) pericardium.

Although so-called stentless valves, comprising a section of xenograft(e.g., porcine) aorta and valve, are available, the most widely usedvalves include some form of artificial leaflet support. One such supportis an elastic “support frame,” sometimes called a “wireform” or “stent,”which has a plurality (typically three) of large radius U-shaped cuspssupporting the cusp region of the leaflets of the bioprosthetic tissue(i.e., either a whole valve or three separate leaflets). The free endsof each two adjacent cusps converge somewhat asymptotically to formupstanding commissures that terminate in U-shaped tips, each beingcurved in the opposite direction as the cusps, and having a relativelysmaller radius. The support frame typically describes a conical tubewith the commissure tips at the small diameter end. This provides anundulating reference shape to which a fixed edge of each leafletattaches (via components such as fabric and sutures) much like thenatural fibrous skeleton in the aortic annulus. Therefore, thealternating cusps and commissures mimic the natural contour of leafletattachment. Importantly, the wireform provides continuous support foreach leaflet along the cusp region so as to better simulate the naturalsupport structure.

The support frame is typically a non-ferromagnetic metal such as ELGILOY(a Co—Cr alloy) that possesses substantial elasticity. A common methodof forming metallic support frames is to bend a wire into a flat(two-dimensional) undulating pattern of the alternating cusps andcommissures, and then roll the flat pattern into a tube using acylindrical roller. The free ends of the resulting three-dimensionalshape, typically in the asymptotic region of the cusps, are thenfastened together using a tubular splice that is plastically crimpedaround the ends. See FIGS. 3 and 4 of U.S. Pat. No. 6,296,662 for asupport frame that is crimped together at a cusp midpoint.

Some valves include polymeric “support frames” rather than metallic, forvarious reasons. For example, U.S. Pat. No. 5,895,420 discloses aplastic support frame that degrades in the body over time. Despite somefavorable attributes of polymeric support frames, for example theability to mold the complex support frame shape, conventional metallicsupport frames are generally preferred for their elastic properties, andhave a proven track record in highly successfully heart valves. Forexample, the CARPENTIER-EDWARDS Porcine Heart Valve and PERIMOUNTPericardial Heart Valve available from Edwards Lifesciences LLC bothhave ELGILOY support frames and have together enjoyed the leadingworldwide market position since 1976.

A conventional heart valve replacement surgery involves accessing theheart in the patient's thoracic cavity through a longitudinal incisionin the chest. For example, a median sternotomy requires cutting throughthe sternum and forcing the two opposing halves of the rib cage to bespread apart, allowing access to the thoracic cavity and heart within.The patient is then placed on cardiopulmonary bypass which involvesstopping the heart to permit access to the internal chambers. Such openheart surgery is particularly invasive and involves a lengthy anddifficult recovery period.

Some attempts have been made to enable less traumatic delivery andimplantation of prosthetic heart valves. For instance, U.S. Pat. No.4,056,854 to Boretos discloses a radially collapsible heart valvesecured to a circular spring stent that can be compressed for deliveryand expanded for securing in a valve position. Also, U.S. Pat. No.4,994,077 to Dobbin describes a disk-shaped heart valve that isconnected to a radially collapsible stent for minimally invasiveimplantation.

Recently, a great amount of research has been done to reduce the traumaand risk associated with conventional open heart valve replacementsurgery. In particular, the field of minimally invasive surgery (MIS)has exploded since the early to mid-1990s, with devices now beingavailable to enable valve replacements without opening the chest cavity.MIS heart valve replacement surgery still typically requires bypass, butthe excision of the native valve and implantation of the prostheticvalve are accomplished via elongated tubes or cannulas, with the help ofendoscopes and other such visualization techniques.

Some examples of more recent MIS heart valves are shown in U.S. Pat. No.5,411,552 to Anderson, et al., U.S. Pat. No. 5,980,570 to Simpson, U.S.Pat. No. 5,984,959 to Robertson, et al., U.S. Pat. No. 6,425,916 toGarrison, et al., and PCT Publication No. WO 99/334142 to Vesely.

Although these and other such devices provide various ways forcollapsing, delivering, and then expanding a “heart valve” per se, noneof them disclose much structural detail of the valve itself. Forinstance, the publication to Vesely shows a tissue leaflet structure ofthe prior art in FIG. 1, and an expandable inner frame of the inventionhaving stent posts in FIGS. 3A-3C. The leaflets are “mounted to thestent posts 22 in a manner similar to that shown in FIG. 1.” Likewise,Anderson describes mounting a porcine valve inside of an expandablestent “by means of a suitable number of sutures to form the cardiacvalve prosthesis 9 shown in FIG. 2.” Such general disclosures stop shortof explaining how to construct a valve in a manner that maximizeslong-term efficacy. In particular, the particular means of attaching theleaflets to the MIS stent is critical to ensure the integrity anddurability of the valve once implanted. All of the prior art MIS valvesare inadequate in this regard. Furthermore, use of conventional supportstents or wireforms is difficult in MIS valves because of the need tocompress the valve into a relatively small diameter delivery package,which creates material challenges.

Some MIS valves of the prior art are intended to be used withoutremoving the natural valve leaflets. Sometimes the natural leaflets areheavily calcified, and their removal entails some risk of plaqueparticles being released into the bloodstream. Therefore, some of theMIS valves are designed to expand outward within the annulus and nativeleaflets, and compress the leaflets against the annulus. The relativelyuneven surface of the calcified annulus and leaflets creates sizingproblems and may complicate the delivery and placement steps. Prior artMIS valves are essentially tubular stents embellished with a nativexenograft valve. The implant methodology is simply the conventionalballoon expansion technique or pushing a self-expanding version from theend of a catheter. Minimal control over the placement of the valve isprovided or contemplated.

Despite some advances in MIS valve design, there remains a need for anMIS valve that is durable and which has a more flexible delivery andimplantation methodology.

SUMMARY OF THE INVENTION

The present invention provides improved prosthetic heart valves that canbe implanted in a minimally-invasive manner, but which also has aspectsthat make it useful for conventional surgeries. The valves and implanttools and methods described herein provide a highly adaptive and simpleto use endovascular delivery option for cardiac surgeons orcardiologists because of features that facilitate implantation. Thevalve is designed to be expelled from a delivery tube in an implant areaand then expanded and/or positioned to contact the surrounding tissuewithout additional anchoring structures. Further, the valve and implanttools permit repositioning and even recollapse of the valve if needed.

In accordance with a first aspect of the invention, a prosthetic heartvalve support frame comprises a leaflet frame and three cusppositioners. The leaflet frame has a continuous, undulating shape thatmimics the natural fibrous structure of an aortic valve. The leafletframe has three cusp regions alternating with and intermediate threecommissure regions, the three cusp regions being positioned at an inflowend of the support frame and circumferentially about a flow axis definedwithin the support frame. The three commissure regions are positioned atan outflow end of the support frame and circumferentially about the flowaxis. The three cusp positioners are rigidly fixed with respect to theleaflet frame and are disposed circumferentially about the flow axis.Each cusp positioner is located at the outflow end of the support frameand intermediate two of the commissure regions of the leaflet frame.

The leaflet frame and the cusp positioners may be formed integrally as asingle piece. Desirably, the support frame is formed by a processcomprising providing a two-dimensional blank of the support frame, andforming the two-dimensional blank into the three-dimensional heart valvesupport frame. The leaflet frame and the cusp positioners may be made ofNitinol, preferably with a martensitic transition temperature of lessthan about 5° C. and an austenitic transition temperature of more thanabout 20° C.

Each cusp positioner of the heart valve support frame desirably has aU-shape with an apex of the U-shape pointing toward the outflow end ofthe support frame and two legs of the U-shape pointing toward the inflowend. Each of the two legs of each U-shaped cusp positioner may berigidly fixed to the continuous leaflet frame at a locationapproximately midway between a cusp region and a commissure regionthereof. An anti-migration member such as an elongated sectionterminating in an enlarged and rounded head can be rigidly fixed to eachcusp positioner to project therefrom. The cusp positioners may flareoutwardly from the rest of the support frame to better contactsurrounding tissue.

The support frame further may include three cusp connectors rigidlyfixed with respect to the leaflet frame and disposed circumferentiallyabout the flow axis. Each cusp connector is located at the inflow end ofthe support frame and intermediate two of the cusp regions of theleaflet frame. Each cusp connector desirably has a U-shape with an apexof the U-shape pointing toward the inflow end of the support frame andtwo legs of the U-shape pointing toward the outflow end. In a preferredembodiment, the leaflet frame, cusp positioners, and cusp connectors areformed integrally as a single piece, and the three cusp positioners andthree cusp connectors define a continuous, undulating shape thatgenerally mimics the shape of the leaflet frame but is rotated 60° aboutthe flow axis therefrom.

Another aspect of the invention is a collapsible prosthetic heart valvethat has a collapsible leaflet frame, three separate, flexible leafletsattached to the leaflet frame, and three cusp positioners rigidly fixedwith respect to the leaflet frame. The leaflet frame has three cuspregions intermediate three commissure regions, the three cusp regionsbeing positioned at an inflow end of the leaflet frame andcircumferentially about a flow axis defined within the support frame.The three commissure regions are positioned at an outflow end of theleaflet frame and circumferentially about the flow axis. Each flexibleleaflet has an arcuate cusp edge opposite a free edge and a pair ofcommissure edges therebetween. The leaflets attach around the leafletframe with the cusp edge of each leaflet extending along one of the cuspregions, and a commissure edge of each leaflet meeting a commissure edgeof an adjacent leaflet at one of the commissure regions. The three cusppositioners are rigidly fixed with respect to the leaflet frame and aredisposed circumferentially about the flow axis, each cusp positionerbeing located at the outflow end of the leaflet frame and intermediatetwo of the commissure regions of the leaflet frame.

The heart valve may incorporate the aforementioned features of thesupport frame, for example a leaflet frame with a continuous, undulatingshape that mimics the natural fibrous structure of an aortic valve, cuspconnectors, and anti-migration members on each cusp positoiner.Desirably, an inflow periphery of the heart valve is defined alongalternating and rigidly fixed cusp regions and cusp connectors. Theinflow periphery may have an external fabric covering, and the heartvalve may further includes a fabric panel defining an exterior surfaceof the heart valve between each pair of cusp positioner and cuspconnector. Preferably, the leaflet frame has a fabric covering alongsubstantially its entire length, the fabric covering defining a flange,and wherein the arcuate cusp edges of the flexible leaflets attach tothe fabric covering flange. The fabric covering flange may projectgenerally outward from the leaflet frame such that the cusp edges of theflexible leaflets extend radially outward past and underneath theleaflet frame to be sewn to the fabric covering flange. Each flexibleleaflet may have a pair of tabs extending on either side of its freeedge, wherein two tabs of adjacent flexible leaflets meet and passtogether to the outside of the adjacent commissure region of the leafletframe and are attached thereto using sutures through the tabs.

In accordance with a still further aspect of the invention, acollapsible prosthetic heart valve comprises:

-   -   a continuous, collapsible leaflet frame having three U-shaped        cusp regions intermediate three U-shaped commissure regions, the        three cusp regions being positioned at an inflow end of the        leaflet frame and circumferentially about a flow axis defined        within the leaflet frame, the three commissure regions being        positioned at an outflow end of the leaflet frame and        circumferentially about the flow axis;    -   a cloth covering extending around the leaflet frame; and    -   three separate, flexible leaflets attached to the leaflet frame,        each leaflet having an arcuate cusp edge opposite a free edge        and a pair of commissure edges therebetween, the leaflets being        attached around the leaflet frame with the cusp edge of each        leaflet extending along one of the cusp regions, and a        commissure edge of each leaflet meeting a commissure edge of an        adjacent leaflet at one of the commissure regions, the        commissure edges of each leaflet further including a tab,        wherein the tabs of two adjacent leaflets extend through the        U-shape commissure region, diverge on the outside of commissure        region, and are attached to the leaflet frame on the outside of        the commissure region.

The present invention also encompasses a method of implanting aprosthetic aortic heart valve with a first step of providing acollapsible prosthetic heart valve having a collapsible leaflet framedefined by three cusp regions on an inflow end of the valve intermediatethree commissure regions on an outflow end of the valve. The valveincludes three cusp positioners on the outflow end and intermediate thethree commissure regions. The method includes collapsing the prostheticheart valve within a delivery tube, advancing the prosthetic heart valvewithin the delivery tube to an aortic annulus, expelling the prostheticheart valve from the delivery tube by relative movement therebetween,expanding the prosthetic heart valve, and positioning the prostheticheart valve such that the cusp positioners contact the two coronary andone non-coronary sinuses of the ascending aorta without blocking thecoronary ostia.

The method preferably includes the step of connecting a holder havingflexible members to the commissure regions of the prosthetic heart valveand utilizing the flexible members to perform the step of positioningthe prosthetic heart valve. Flexible members of the holder may also beconnected to the cusp positioners and utilized to perform the step ofpositioning the prosthetic heart valve, or to rotate the prostheticheart valve during the step of positioning. Advantageously, the flexiblemembers may be used to re-collapse the prosthetic heart valve after thestep of expanding. The prosthetic heart valve is desirably expanded in alocation that is inferior to a final implant position such that the cusppositioners contact the surrounding aortic annulus, and the step ofpositioning comprises displacing the valve in a superior direction to afinal implant position. The cusp positioners may be flared outward todefine a circle about a flow axis of the valve greater than a circleabout the flow axis defined by the three commissure regions, such thatthe step of displacing the valve in a superior direction causes theoutwardly flared cusp positioners to be channeled into perspectivecoronary sinuses.

In accordance with a preferred method, the collapsible leaflet frame isformed of a shape memory alloy having a martensitic transitiontemperature less than room temperature, and an austenitic transitiontemperature less than body temperature, and the step of collapsing isdone with the material of the leaflet frame at a temperature less thanits martensitic transition temperature. For example, the step ofcollapsing may be done in conjunction with immersing the prostheticheart valve in an ice bath to reduce the temperature of the material ofleaflet frame to below its martensitic transition temperature. Inanother aspect, the collapsible leaflet frame may be formed of a shapememory alloy having a memory condition in its expanded state, andwherein the step of expanding the prosthetic heart valve comprises bothpermitting self-expansion of the valve to an intermediate diameter andthen using a physical expander to increase the diameter of the valve tothe memory condition of the leaflet frame.

A further method of implanting a collapsible prosthetic heart valveprovided by the present invention comprises first providing aself-expanding valve comprised of a material displaying hysteresis inthe elastic or superelastic region. The valve is permitted toself-expand to a first diameter, and then the valve is assisted with aphysical expander such as a balloon to further expand to a seconddiameter.

The prosthetic heart valve may includes a collapsible leaflet frameformed of a shape memory alloy having a martensitic transitiontemperature less than room temperature and an austenitic transitiontemperature less than body temperature, and the method may furtherinclude a step of collapsing the valve with the material of the leafletframe at a temperature less than its martensitic transition temperature.Fir example, the step of collapsing may be done in conjunction withimmersing the prosthetic heart valve in an ice bath to reduce thetemperature of the material of leaflet frame to below its martensitictransition temperature.

The prosthetic heart valve may have a collapsible leaflet frame definedby three cusp regions on an inflow end of the valve intermediate threecommissure regions on an outflow end of the valve, and three cusppositioners on the outflow end and intermediate the three commissureregions. In this case, the method may further include:

-   -   collapsing the prosthetic heart valve within a delivery tube;    -   advancing the prosthetic heart valve within the delivery tube to        an aortic annulus;    -   expelling the prosthetic heart valve from the delivery tube by        relative movement therebetween;    -   expanding the prosthetic heart valve by the steps of permitting        self-expansion and assisting further expansion; and    -   positioning the prosthetic heart valve such that the cusp        positioners contact the two coronary and one non-coronary        sinuses of the ascending aorta without blocking the coronary        ostia.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a partial view of a patient's heart generally verticallysection through the left ventricle and associated heart valves, andillustrating the implantation approach of a catheter-based prostheticvalve of the present invention;

FIG. 2A is a vertical sectional view through an aortic annulus and anexemplary prosthetic heart valve of the present invention implantedtherein;

FIG. 2B is a top plan view of the implanted prosthetic heart valve ofFIG. 2A;

FIGS. 3A-3C are perspective, top plan, and bottom plan views,respectively, of the prosthetic heart valve of FIG. 2A;

FIG. 4 is a plan view of a prosthetic heart valve support frame of thepresent invention in a two-dimensional blank,form prior to conversion tothree-dimensional final form;

FIG. 5 is a perspective view of the prosthetic heart valve support frameof FIG. 4 in its three-dimensional final form with a leaflet frame andcusp positioners;

FIGS. 5A and 5B are views of a portion of the three-dimensional heartvalve support frame of FIG. 5 showing alternative cusp positionerconfigurations;

FIG. 6A is an elevational view of a partially assembled prosthetic heartvalve as in FIGS. 3A-3C;

FIG. 6B is an elevational view of the prosthetic heart valve of FIG. 6Afully assembled;

FIG. 7 is a plan view of an exemplary leaflet used in the prostheticheart valves of the present invention;

FIG. 8 is a partial sectional view of a commissure region of theexemplary prosthetic heart valve taken along line 8-8 of FIG. 3B;

FIG. 9 is a sectional view through a portion of the support frame of theexemplary prosthetic heart valve, taken along line 9-9 of FIG. 8;

FIG. 10 is a sectional view through a commissure tip region of theexemplary prosthetic heart valve, taken along line 10-10 of FIG. 8;

FIG. 11 is a schematic perspective view of a prosthetic heart valvesupport frame of the present invention being loaded into a deliverycatheter;

FIG. 12 is a perspective view of the support frame after having beenloaded into a delivery catheter;

FIGS. 13A-13B are perspective and elevational views of an exemplarycompressible/expandable heart valve holder attached to a prostheticheart valve of the present invention;

FIG. 14 is a perspective view of the expulsion of an assembledprosthetic heart valve and holder as in FIGS. 13A and 13B from thedistal end of a delivery catheter;

FIG. 15 is a bottom plan view of an exemplary compressible/expandableheart valve holder of the present invention;

FIG. 16 is a plan view of a multi-armed flexible portion of the holderof FIG. 15; and

FIGS. 17A-17B are two views of a rigid portion of the holder of FIG. 15.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present invention provides an improved minimally invasive (MIS)valve support frame, MIS valve, and methods of construction and deliveryas described herein and shown in the accompanying drawings.

The invention pertains primarily to flexible leaflet heart valves andinternal support frames, which are also referred to in the art as stentsor wireforms. As mentioned above, the flexible leaflets can be formedfrom biological (e.g., bovine pericardium) or synthetic material. Inthis context, a “support frame” for a flexible leaflet heart valveprovides the primary internal structural support for the leaflets, andsubstantially mimics the natural fibrous skeleton of the respectivevalve annulus. More specifically, each of the leaflets has an outer edgethat is coupled to a portion of the support frame such that its inneredge is free to move within the orifice area of the valve, thusproviding the opening and closing surfaces thereof. A biologicalxenograft valve can be used to provide the flexible leaflets in thevalves of the present invention, though the internal support frame isparticularly suited to receive individual leaflets.

The leaflet frames of the present invention have a continuous,undulating shape with three arcuate or U-shaped cusp regions on theinflow end separated by three upstanding and generally axially-orientedarcuate or U-shaped commissure regions on the outflow end. Around thecircumference of the leaflet frame, the shape has an alternatingstructure of cusp-commissure-cusp-commissure-cusp-commissure, andgenerally describes a conical surface of revolution with the threecommissures on the outflow end of the valve being closer together thanthe three cusps. Some support frames may alternatively describe atubular surface of revolution about an axis. The cusp regions andcommissure regions are evenly distributed about a flow axis through thesupport frame, and therefore the three cusp regions are 120° apart fromeach other, and each of the three commissure regions is 120° apart fromthe next and 60° from the adjacent cusp regions.

The term “continuous” to describe the heart valve leaflet frame meansthat a single continuous and closed-shape line (i.e., loop) can be drawnfollowing the sequential cusp and commissure regions, and “undulating”refers to the serpentine or alternating sinusoidal character of theline. More generally, a continuous, undulating heart valve leaflet frameapproximates the shape of the natural fibrous tissue around the aorticvalve annulus so as to mimic that natural support structure for optimumfunctionality of the prosthetic leaflets.

The present invention primarily pertains to prosthetic heart valvessuitable for minimally invasive delivery and implantation. Suchminimally invasive valves are capable of being compressed or collapsedinto a small profile and delivered through a catheter or cannula (atube) to the site of implantation for remote expansion and anchoringthereto. It should be understood, however, that certain aspects of theinvention described herein are beneficial for prosthetic heart valves ingeneral, and thus not all of the claims should be construed to require aminimally invasive valve.

FIG. 1 depicts a portion of a heart of a patient with the left ventricleLV, aortic valve AV, mitral valve MV, and ascending aorta AA shown insection. A delivery catheter or tube 20 is seen in position just priorto complete expulsion and expansion of a prosthetic heart valve 22 froma distal end thereof for implant at the aortic valve AV annulus. Theaortic valve AV leaflets L may first be excised prior to implant of thevalve 22, or more preferably the leaflets L remain in place and areexpanded outward and compressed against the lumen of the aortic valve AVannulus upon expansion of the valve. The distal end of the delivery tube20 may optionally be stabilized by a balloon 24 (shown in phantom)inflated against the lumen of the ascending aorta AA, or through othermeans. The delivery tube 20 is preferably inserted in the vasculature ofthe patient using a larger diameter introducer 26 through a peripheralvessel such as the femoral artery or femoral vein. Alternatively, theperipheral vessel may be the internal jugular vein, the subclavianartery, the axillary artery, the abdominal aorta, the descending aorta,or any other suitable blood vessel. The introducer 26 may be inserted bysurgical cut down or percutaneously using the Seldinger technique.

FIGS. 2A and 2B illustrate the prosthetic heart valve 22 implanted atthe aortic valve AV annulus. The heart valve 22 includes three cusps 30on an inflow end (one of which is not visible) and three commissures 32on an outflow end. The direction of blood flow BF is indicated with anarrow in the ascending aorta AA. The natural leaflets are desirablycompressed against the lumen of the aortic valve annulus by theprosthetic heart valve 22, as seen in FIG. 2B. The valve 22 is orientedabout a flow axis such that the commissures 32 are generally alignedwith the native commissures C, while the cusps (not shown butintermediate the commissures 32) are generally aligned with the naturalcusps/leaflets L. The heart valve 22 contacts the lumen wall of theaortic valve AV annulus and desirably retains its position due tofriction therebetween. In this regard, the heart valve 22 expands fromits delivery configuration shown in FIG. 1 to the expanded configurationin FIGS. 2A and 2B.

The valve 32 contacts the lumen wall around the entire periphery of theinflow end thereof and in certain areas adjacent to the inflowperiphery, as will be explained below. The inflow periphery is definedby the lower ends of the cusps 30 as well as by the lower ends of threecusps connectors 40 that extend between and fill the gaps between thecusps 30. Additionally, the heart valve 22 includes three cusppositioners 42, two of which are visible in FIG. 2A, that are rigidlyfixed with respect to an internal valve support frame and are eachlocated generally at the outflow end of the valve intermediate two ofthe commissures 32. With reference to FIG. 2B, the cusp positioners 42are evenly distributed about a central flow axis 44, and when implantedalign with the native leaflets L. The cusp positioners 42 preferablyextend radially farther outward than the commissures 32 and compress theleaflets L against the natural sinus cavities formed just above theaortic valve AV annulus. Coronary ostia CO open from two of the threesinus cavities, as seen in FIG. 2A, and the cusp positioners 42 aresized and placed by the operator to avoid occluding flow through thecoronary ostia CO. The advantageous structure and function of these cusppositioners 42 will be more fully explained below.

With reference now to FIGS. 3A-3C, the exemplary prosthetic heart valve22 will be more fully described. The shape of an internal support frame50 seen in FIG. 5 generally governs the shape of the valve 22. Asmentioned, the valve 22 includes the aforementioned cusps 30 andcommissures 32 evenly distributed about a flow axis 44. The cusps 30 andcusp connectors 40 define a scalloped inflow periphery of the valve 22,while the outflow periphery is defined by the three commissures 32 andthe three cusp positioners 42. The entire internal support frame 50except for the cusp positioners 42 is covered over with one or morelayers of material, the exterior layer of which is typically a fabric asshown (but not numbered). The use of a fabric such as polyethyleneterephthalate provides a matrix into which surrounding tissue can growto help anchor the valve in place.

Three flexible leaflets 52 mount to the valve 22 in a trifoilconfiguration with free edges 53 thereof arranged to meet or coapt inthe middle of the valve and provide one-way occlusion. An outer edge ofeach leaflet 52 attaches to the valve 22 between two of the commissures32 and around one of the cusps 30. An exemplary structural attachment ofthe leaflets 52 to the internal support frame 50 will be describedbelow.

As mentioned, each cusp connector 40 extends between two of the cusps30. A panel of fabric or other material 54 covers an area between theinflow or lower edge of each cusp connector 40 and the correspondingcommissures 32. Some of this panel of fabric 54 desirably contacts thelumen wall of the aortic valve AV annulus to help prevent leakage aroundthe valve.

The exemplary cusp positioners 42 each have an inverted U-shape with anapex pointed toward the outflow end of the valve 22 and two legsextending generally toward the inflow end and connecting with theremainder of the valve. The term “U-shape” is intended to cover allconfigurations that have two legs and an apex therebetween. Otherfigurative descriptions such as V-shaped, bell-shaped, sinusoidal,arcuate, or the like are therefore encompassed by the term “U-shape”. Itis contemplated, however, that the cusp positioners 42 could assumeother forms, such as a generally linear, cantilevered arm extendingupward from the midpoint of each cusp 30. In whatever form, the cusppositioners 42 provide the valve 22 with three points of contact withthe surrounding tissue that is midway between the three commissures 32so as to help stabilize and anchor the valve in its implant position.Moreover, the cusp positioners 42 desirably perform the function ofcompressing the native leaflets L outward against the sinus cavities, atleast in those procedures where the leaflets L are not excised.

The leaflets L in a diseased valve may be less than flexible, and indeedmay be highly calcified. It is often considered preferable to avoidremoving the leaflets L so as to avoid disturbing the calcification orother stenotic material that has built up around the leaflets.Therefore, the present invention desirably provides structure tocompress the native leaflets L outward against the aortic wall sinuscavities and hold the leaflets in that position so as to avoid flappingand potentially interfering with blood flow through the prostheticvalve. The inverted U-shape of the cusp positioners 42 is believed toprovide effective structure to both anchor the valve in the aortic valveAV annulus and also control, or corral, if you will, the obsolete nativeleaflets L. At the same time, the cusp positioners 42 are relativelyminimal in total area so as to avoid unduly interfering with back flowof blood on the outflow side of each of the leaflets 52, or to thecoronary ostia CO. Therefore, the cusp positioners 42 are desirablydefined by relatively thin members, as shown, as opposed to walls orpanels, or the like. Multiple cusp positioners 42 per valve cusp 30 areconceivable, though the total solid volume taken up by the cusppositioners should be kept to a minimum so as to minimize the risk ofoccluding the coronary ostia CO.

The axial height of the cusp positioners 42 relative to the commissures32 is seen best in FIG. 2A (and in FIG. 6B). Preferably, the commissures32 are slightly taller than the cusp positioners 42, although such anarrangement is not considered mandatory. The main consideration in thesize of the cusp positioners 42 is to avoid occluding the coronary ostiaCO. Therefore, as seen in FIG. 2A, the cusp positioners 42 contact thesurrounding aortic valve AV lumen wall just below the coronary ostia CO.Of course, the anatomy of each patient differs slightly from the next,and the precise position of the coronary ostia CO cannot be predictedwith absolute certainty. Furthermore, the final location of the cusppositioners 42 is dependent on the skill of the cardiac surgeon orcardiologist. In the ideal situation, however, the cusp positioners 42are positioned just below and aligned circumferentially with thecoronary ostia CO as seen in FIGS. 2A and 2B.

FIGS. 2B and 3B-3C illustrate the relative outward radial position ofthe cusp positioners 42 with respect to the commissures 32 therebetween,and with respect to the cusp connectors 40. As seen in the isolated viewof the heart valve support frame 50 in FIG. 5, the cusp positioners 42are angled or flared outward from the remainder of the support frame.This outward flaring helps ensure good contact between the apex of thecusp positioners 42 and the surrounding walls of the aortic valve AVsinus cavities. In this regard, the outer configuration of the heartvalve 22 is designed to maximize contact with the aortic valve AV lumenwall both in the annulus and for a short distance into each sinuscavity. This extensive surface contact between the prosthetic valve 22and the surrounding tissue may obviate the need for sutures, staples,sharp barbs or other such anchoring structure, although such structurecould be used in conjunction with the valve. The valve 22 is merelyexpelled from the end of the delivery tube 20 (FIG. 1), expanded with orwithout assistance of a balloon, and held in place by frictional contactbetween the inflow periphery against the annulus, and between the cusppositioners 42 and the sinus cavities (or intervening native leaflets).

Each cusp positioner 42 further includes at least one anti-migrationmember 56 rigidly fixed thereto and designed to help anchor the supportframe 50 to the surrounding tissue. In the illustrated embodiment, theanti-migration members 56 each preferably includes an elongated section58 terminating in an enlarged and rounded head 60, the configurationthus somewhat resembling a spoon. The anti-migration member 56 desirablyprojects out of the plane defined by the associated cusp positioner 42,and may extend generally axially in the inflow direction from the apexthereof, as seen in FIG. 3A. When the valve 22 is implanted, theanti-migration members 56 are designed to contact and become somewhatentrapped in the native leaflets. Therefore, the anti-migration members56 act as a rounded barb of sorts to maintain the valve 22 in itsimplant position. The members 56 also may help prevent flapping of thenative leaflets in the swirling blood flow. Numerous otherconfigurations are contemplated, the general idea being that theanti-migration member 56 enhances the ability of the associated cusppositioner 42 to anchor to the surrounding tissue. In this regard, theterm “anti-migration member” is meant to include any structure thatenhances such anchoring, including both blunt and sharp structures(i.e., barbs).

Various procedures and apparatuses for converting a two-dimensionalblank such as shown in FIG. 4 to the three-dimensional form of FIG. 5are described in more detail in co-pending U.S. patent application Ser.No. 10/251,651, filed Sep. 20, 2002, and entitled continuous heart valvesupport frame and method of manufacture. In short, the process involvesbending the two-dimensional blank 70 around a cylindrical or conicalmandrel and altering the material so as to retain its three-dimensionalshape. For example, various nickel-titanium alloys (Nitinol) may beeasily bent around a mandrel and then set into that shape using heattreatments.

In an exemplary embodiment of the present invention, the internalsupport frame 50 of the valve 22 is made of a material that is, highlyflexible so as to permit maximum relative movement between the valvecusps and commissures, and in some cases to permit constriction into asmall profile diameter for minimally invasive delivery to animplantation site. At the same time the support frame must possess aminimum amount of stiffness to provide the desired support to theleaflets. Therefore, there is a balance obtained between the requisiteflexibility and stiffness.

The material for the internal support frame is desirably “elastic,”which means that it has the capacity to rebound from imposed strain.Various NITINOL alloys are especially suitable for making the internalsupport frame of the present invention as in certain circumstances theyare considered to be “superelastic.” Other materials that may be usedinclude ELGILOY, titanium, stainless-steel, even polymers, and similarexpedients. These latter materials do not display superelasticity butare still elastic. Other materials may fit within this definition butthey must be suitable for long-term implantation in the body.

The term “superelastic” (sometimes “pseudoelastic”) refers to thatproperty of some materials to undergo extreme strains (up to 8%) withoutreaching their failure stress limit. Some so-called shape memory alloys(SMAs) are known to display a superelastic phenomena or rubber-likebehavior in which a strain attained beyond the elastic limit of the SMAmaterial during loading is recovered during unloading. This superelasticphenomenon occurs when load is applied to an austenitic SMA articlewhich first deforms elastically up to the yield point of the SMAmaterial (sometimes referred to as the critical stress). Upon thefurther imposition of load, the SMA material begins to transform intostress-induced martensite or “SIM.” This transformation takes place atessentially constant stress, up to the point where the SMA material iscompletely transformed into martensite. When the stress is removed, theSMA material will revert back into austenite and the article will returnto its original, pre-programmed programmed or memorized shape.

The support frame 50 is desirably constructed of a material thatexhibits hysteresis in the elastic and/or superelastic region.“Hysteresis” indicates that when the material is strained beyond the“memory condition” (defined as unconstrained geometry) it produces astress-strain curve that is different and higher than the stress-straincurve produced as the material attempts to return to its memorycondition. An example of a material that exhibits such a hysteresis isNITINOL. The presence of this hysteresis implies that it requires agreater force to displace the material form its memory condition thanthe material exerts as it recovers to its memory condition.

When using NITINOL the shape set is done at a particular temperature fora period of time designed to ensure certain properties in the material.Namely, the martensitic transition temperature is desirably less thanroom temperature and the austenitic transition temperature is desirablyless than body temperature. For instance, the temperature below whichthe material is in martensitic form is around 0-5° C., while thetemperature above which the material is in austenitic form is around20-25° C. When the material is shape set in this way, the heart valve 22can be cooled, such as in an ice bath, just prior to implant to changethe crystalline structure of the support frame 50 to martensite andcreate high flexibility so as to enable compaction thereof into a smalldiameter delivery profile. After implant and expansion, the temperaturerises from body heat above the austenitic transition temperature andthus the support frame 50 possesses the desired degree of stiffness toproperly support the leaflets.

The support frame 50 (and blank 70) includes a leaflet frame 72 definedby three cusp regions 74 intermediate three commissure regions 76. InFIG. 4 the leaflet frame 72 in the blank 70 exhibits a three-leaf clovershape, while in FIG. 5 the leaflet frame 72 has a continuous, undulatingshape as described above. A second three-leaf clover shape can be seenin FIG. 4 formed by the three cusp connectors 40 and three cusppositioners 42. When bent into the three-dimensional configuration ofFIG. 5, two continuous, undulating shapes can be seen oriented 60° withrespect to one another about the central flow axis. Each cusp connector40 includes an apex 80 and a pair of legs 82 that rigidly attach to theleaflet frame 72 at junction points 84. Likewise, each cusp positioner42 includes an apex 90 and a pair of legs 92 that rigidly attach to theleaflet frame 72 at junction points 94. In the preferred and illustratedembodiment, the junction points 84 and 94 are coincident.

FIGS. 5A and 5B show alternative cusp positioner configurations for thethree-dimensional heart valve support frame 50 of FIG. 5. As mentionedabove, the anti-migration members facilitate anchoring of the supportframe 50 to the surrounding anatomy, and prevent axial and rotationalmovement of the valve 22. The anti-migration members 56 shown in FIG. 5project generally axially in the inflow direction from the apex 90 ofeach cusp positioner 42. In FIG. 5A, a second anti-migration member 57projects generally axially in the outflow direction from the apex 90 ofeach cusp positioner 42. In FIG. 5B, there are multiple anti-migrationmembers 56 extending generally axially in the inflow direction. Variouscombinations, placements and orientations of these examples arecontemplated, and the examples should not be considered limiting.

FIG. 6A shows the valve 22 almost completely assembled, but without theaforementioned cloth covers 54 that are seen in the fully assembledvalve of FIG. 6B. The covers 54 help prevent leakage of blood around theimplanted valve 22, and specifically in the areas between the each pairof cusps 30.

FIG. 7 illustrates an exemplary leaflet 52 in plan view. The free edge50 is shown as linear, but may also be arcuate, angled, trapezoidal, orother configuration. Each leaflet includes a pair of opposed generallyrectangular tabs 100 at either end of the free edge 53. An arcuate cuspedge 102 extends between the tabs 100 and opposite the free edge 53. Thetabs 100 and arcuate cusp edge 102 are secured to the valve 22, andspecifically along the contours of the leaflet frame 72 seen in FIG. 5.

FIG. 8 is an enlarged cutaway view of one of the commissures 32 of thevalve 22 taken along line 8-8 of FIG. 3B and showing the internalconstruction thereof. The commissure region 76 of the leaflet frame 72tapers down in the outflow direction to a closed tip 104. Attachmentflanges 106 are formed adjacent the tip 104 and desirably include aplurality of assembly holes 108 sized to permit passage of suturestherethrough. The adjacent leaflets 52 come together in the commissureregions 76 and the tabs 100 thereof are folded away from each other onthe exterior of the flanges 106.

As seen in FIG. 9, the cusp edge 102 of each leaflet 52 attaches withsutures 110 to a cloth flange 112 of a tubular fabric cover 114 aroundthe leaflet frame 72. This configuration causes tensile forces impartedby the leaflets 52 to be transferred as much as possible to the frame 72rather than being primarily borne by the attachment sutures 110.

FIG. 10 shows the attachment structure at the commissure tip 104, andspecifically illustrates sutures 120 passing through the fabric cover114, through the assembly holes 108, and through the folded leaflet tabs100. A second suture 122 passes through the cloth flange 112, theleaflet tab 100, and cloth covers 54 (also shown in FIG. 6B). Becauseeach of the leaflets 52 includes the tab 100 that extends to the outsideof the leaflet frame 72, high forces that are seen with closing of thevalve are less likely to pull the sutures 120 through the tabs. That is,the construction shown in FIG. 10 causes tensile forces imparted by theleaflets 52 to be transferred as much as possible from the sutures 120,122 to the frame 72, thus helping to prevent tearing of the flexibleleaflets and rendering the valve 22 more durable.

FIGS. 11 and 12 schematically illustrate a technique for loading aprosthetic heart valve of the present invention into a delivery tube.For the sake of clarity, only the support frame 50 is shown being loadedinto the delivery tube 20. A plurality of sutures or other such flexiblemembers or filaments 130 are shown looped through each of the commissureregions 76 of the support frame 50. These filaments 130 extend into thedistal end of the delivery tube 20 and through its lumen to a proximalend (not shown) where they are connected to a tensioning device. Inactual use, the filaments 130 would be threaded through the commissures32 of the valve 22, avoiding the flexible leaflets. A loading adapter132 couples to the distal end of the delivery tube 20. The adapter 132includes an inner funnel-shaped opening 134. Tension on the filaments130 pulls the commissures 32 of the valve into the funnel-shaped opening134 which gradually compresses the valve into a diameter smaller thanthe lumen of the delivery tube 20. Once the valve 22 is positioned fullywithin the delivery tube 20, as seen in FIG. 12, the filaments 130 andadapter 132 are removed.

FIGS. 13-17 illustrate a minimally invasive holder for use with theprosthetic heart valves of the present invention. FIGS. 13A and 13B showthe holder 150 attach to the heart valve 22 as described above. Theholder 150 includes a multi-armed flexible portion 152 and a rigidportion 154 (seen in FIGS. 17A-17B). The flexible portion 152 includes aplurality, at least three, but preferably six flexible members or arms156 extending outward from a central circular disk 158. Each of the arms156 terminates in a rounded end having an attachment aperture 160. Thearms 156 are distributed evenly about the circumference of the circulardisk 158, and are arrayed to attach to each of the commissures 32 andcusp positioners 42 of the valve 22. Releasable sutures 162 or othersuch attachment structure are used for this purpose.

FIG. 14 shows the assembled holder 150 and valve 22 emerging from thedistal end of a delivery tube 20. Prior to this stage, the flexiblemembers or arms 156 are oriented generally axially within the tube 20with the valve 22 also collapsed and having its outflow prongs coupledto the distal ends of the arms 156. The arms 156 of the holder 150 aresufficiently flexible to be compressed into the small profile requiredfor delivery through the delivery tube 20. In this regard, the flexibleportion 152 is desirably made of Nitinol. A handle 170 which may beflexible or rigid attaches to the holder 150 for manipulation thereof.Displacing the handle 170 in a distal direction with respect to the tube20 therefore expels the valve/holder combination and the resiliency ofthe valve 22 and holder arms 156 causes them to spring outward. Itshould be understood that other designs of the holder 150 may beutilized, such as replacing the spring-like arms 156 with rigid membersthat are hinged and spring-biased.

FIGS. 15-17 illustrate specifics of the exemplary flexible portion 152and rigid portion 154. In a relaxed configuration, the flexible portion152 is planar, and maybe cut from a sheet of Nitinol. The rigid portion154 includes a proximal face 180 that is sized approximately the same asthe circular disk 158, and small enough to fit within the delivery tube20. A central threaded bore 182 opens to the proximal face 180 forreceiving the handle 170. FIG. 15 illustrates a number of sutures 162threaded through the holder 150 and used to couple the holder to the sixoutflow prongs of the prosthetic heart valve 22. Desirably, thesesutures 162 are anchored with respect to the holder and each one passesover a cutting guide in the holder such that the suture may be severedalong its midpoint. resulting in two free ends that can be pulled freeof the valve.

The holder 150 is sufficiently flexible to be compressed into a smallprofile and passed through the delivery tube 20. At the same time, theflexible portion 152 and multiple flexible arms 156 have a sufficientdegree of torsional strength to permit the operator to rotate the valve22 during the implant procedure. Furthermore, the arms 156 are shaped tocontact the distal mouth of the delivery tube 20 when the assembly ispulled toward the tube which, due to their radial stiffness, causes thearms to bend back toward their axial orientation within the tube. Sincethe distal ends of the arms are coupled to at least three of the outflowprongs of the prosthetic heart valve 22, the valve constrictsaccordingly. Constriction of the valve 22 after having been fullyexpelled from the end of the delivery tube and expanded permitsrepositioning of the valve 22. That is, the cusp positioners 42 aredesigned to contact the sinuses cavities or aortic wall after the valve22 expands, and the retraction/constriction option afforded by theholder 150 may be necessary to disengage the cusp positioners from thesurrounding tissue to reposition or re-orient the valve. Furthermore,the valve 22 can be completely collapsed and retracted back into thedelivery tube to permit removal in case the surgeon or cardiologistdeems the valve unsuitable for whatever reason.

Method of Use

Prior to implant, the cardiac surgeon or cardiologist measures theaortic valve AV annulus using appropriate sizers, minimally invasive ornot as the case may be, a number of which are available and which willnot be further described herein. The correctly sized valve is thenselected and compressed into the delivery catheter or tube 20, such aswith the use of the loading adapter 132 having the inner funnel-shapedopening 134 as seen in FIG. 11. To facilitate this loading step, theinner support frame 50 of the valve 20 must be able to withstand highstresses without failure. One method is to form the support frame 50from a material that has superelastic properties, for instance a Nitinolthat has a martensitic transition temperature of less than about 5° C.can be immersed in an ice bath to change its crystalline structure tomartensite, which is a superelastic phase. Once loaded into the deliverytube 20, the support frame 50 will not revert back to its original shapeupon a temperature rise and thus does not exert undue outward force onthe tube. The heart valve 22 may be loaded around an inflation balloon,but for the sake of a small profile the balloon is used after expulsionof the valve from the tube at the implantation site.

With reference again to FIG. 1, the delivery tube 20 is seen in positionjust prior to complete expulsion and expansion of the prosthetic heartvalve 22 from a distal end thereof for implant at the aortic valve AVannulus. The distal end of the delivery tube 20 may optionally bestabilized by a balloon 24 (shown in phantom) inflated against the lumenof the ascending aorta AA, or through other means. The delivery tube 20is preferably inserted in the vasculature of the patient using a largerdiameter introducer 26 through a peripheral vessel such as the femoralartery or femoral vein. Alternatively, the peripheral vessel may be theinternal jugular vein, the subclavian artery, the axillary artery, theabdominal aorta, the descending aorta, or any other suitable bloodvessel. The introducer 26 may be inserted by surgical cut down orpercutaneously using the Seldinger technique.

The prosthetic heart valve 22 is expelled from the delivery tube 20 byrelative movement therebetween—i.e., by pushing the valve from the tubeor by retracting the tube from around the valve. The valve 22 desirablyself-expands into contact with the surrounding lumen wall, but may alsobe assisted with an inflation balloon or other such physical expander.

With reference to FIGS. 2A and 2B, the cusps positioners 42 help guidethe prosthetic heart valve 22 into position in the aortic valve AVannulus. As mentioned above, the cusp positioners 42 desirably flareoutward from the rest of the valve structure and are thus configured tocontact the sinuses of the aortic valve AV while the cusps 30 are sizedto fit within the annulus. In accordance with one method ofimplantation, the surgeon or cardiologist expels the heart valve 22below (i.e., toward the left ventricle) its optimum implant position,and then axially displaces the valve upward into the desired position.Stated another way, the heart valve 22 is expanded in a location that isinferior to a final implant position such that the cusp positioners 42contact the surrounding aortic annulus, and the valve is thenrepositioned by displacing the valve in a superior direction to a finalimplant position. As the valve 22 ascends, the cusp positioners 42spring outward into the three valve sinuses and help rotationally orientthe valve. That is, the sinuses channel the cusp positioners 42 andcorrect any rotational misalignment. Finally, the valve 22 is implantedwith the cusp positioners 42 in the sinus cavities (preferably below thecoronary ostia CO) and the cusps 30 and cusp connectors 40 forming ascalloped yet continuous contact wall against the aortic valve AVannulus or root.

As mentioned, a physical expander (e.g., balloon) may be used toradially outwardly expand the valve 22 (including the internal supportframe 50) beyond its self-expanded diameter so that it is firmlyanchored in place. A prosthetic valve possessing hysteresis that is heldin a reduced (first or constrained) diameter will exert an outwardradial force that is less than the force at which it will resist aninward radial force. Therefore, if deployed in-situ, the device is notexpected to exert enough force on the vessel wall to expand to thedesired diameter. However, if the expansion is assisted by means of aballoon or other physical expander, the hysteresis of the material willallow it to better maintain its diameter once that diameter is achieved.This is unlike a self-expanding device that relies solely on the outwardradial force of the device to achieve its desired diameter. It is alsounlike balloon expanded devices that rely on a balloon to plasticallydeform the device into the desired diameter. Although it is conceivablethat a balloon or other physical expander could be used in aself-expanding device made of a material that does not display ahysteresis, the benefits would not be as great.

It will be appreciated that the invention has been described hereabovewith reference to certain examples or preferred embodiments as shown inthe drawings. Various additions, deletions, changes and alterations maybe made to the above-described embodiments and examples, and it isintended that all such additions, deletions, changes and alterations beincluded within the scope of the following claims.

1. A collapsible prosthetic heart valve, comprising: a collapsibleleaflet frame having an inflow end and an outflow end and three cuspregions intermediate three commissure regions, the three cusp regionsbeing positioned at the inflow end of the leaflet frame andcircumferentially about a flow axis defined within the support frame,the three commissure regions being positioned at the outflow end of theleaflet frame and circumferentially about the flow axis; three separate,flexible leaflets attached to the leaflet frame, each leaflet having anarcuate cusp edge opposite a free edge and a pair of commissure edgestherebetween, the leaflets being attached around the leaflet frame withthe cusp edge of each leaflet extending along one of the cusp regions,and a commissure edge of each leaflet meeting a commissure edge of anadjacent leaflet at one of the commissure regions; and three cusppositioners integrally attached to the leaflet frame and disposedcircumferentially about the flow axis, at least a portion of each cusppositioner being located adjacent to a flexible leaflet and axiallypositioned between the free edge and cusp edge of the flexible leaflet,the three cusp positioners extending radially farther outwardly than thethree commissure regions and configured for engagement with nativeleaflets of a heart valve; wherein each cusp positioner has a U-shapewith an apex of the U-shape pointing toward the outflow end of theleaflet frame and two legs of the U-shape pointing toward the inflowend.
 2. The heart valve of claim 1, wherein each of the two legs of eachU-shaped cusp positioner is rigidly fixed to the collapsible leafletframe at a location approximately midway between a cusp legion and acommissure region thereof.
 3. The heart valve of claim 1, furtherincluding an anti-migration member rigidly fixed to each cusp positionerand projecting therefrom.
 4. A collapsible prosthetic heart valve,comprising: a collapsible leaflet frame having an inflow end and anoutflow end and three cusp regions intermediate three commissureregions, the three cusp regions being positioned at the inflow end ofthe leaflet frame and circumferentially about a flow axis defined withinthe support frame, the three commissure regions being positioned at theoutflow end of the leaflet frame and circumferentially about the flowaxis; three separate, flexible leaflets attached to the leaflet frame,each leaflet having an arcuate cusp edge opposite a free edge and a pairof commissure edges therebetween, the leaflets being attached around theleaflet frame with the cusp edge of each leaflet extending along one ofthe cusp regions, and a commissure edge of each leaflet meeting acommissure edge of an adjacent leaflet at one of the commissure regions;and three cusp positioners integrally attached to the leaflet frame anddisposed circumferentially about the flow axis, at least a portion ofeach cusp positioner being located adjacent to a flexible leaflet andaxially positioned between the free edge and cusp edge of the flexibleleaflet, the three cusp positioners extending radially farther outwardlythan the three commissure regions and configured for engagement withnative leaflets of a heart valve; wherein the heart valve furtherincludes three cusp connectors rigidly fixed with respect to the leafletframe and disposed circumferentially about the flow axis, each cuspconnector being located at the inflow end of the leaflet frame andintermediate two of the cusp regions of the leaflet frame; wherein eachcusp connector has a U-shape with an apex of the U-shape pointing towardthe inflow end of the leaflet frame and two legs of the U-shape pointingtoward the outflow end.
 5. The heart valve of claim 4, wherein theleaflet frame, cusp positioners, and cusp connectors are formedintegrally as a single piece, and wherein the three cusp positioners andthree cusp connectors define a continuous, undulating shape thatgenerally mimics the shape of the leaflet frame but is rotated 60° aboutthe flow axis therefrom.
 6. A collapsible prosthetic heart valve,comprising: a collapsible leaflet frame having an inflow end and anoutflow end and three cusp regions intermediate three commissureregions, the three cusp regions being positioned at the inflow end ofthe leaflet frame and circumferentially about a flow axis defined withinthe support frame, the three commissure regions being positioned at theoutflow end of the leaflet frame and circumferentially about the flowaxis; three separate, flexible leaflets attached to the leaflet frame,each leaflet having an arcuate cusp edge opposite a free edge and a pairof commissure edges therebetween, the leaflets being attached around theleaflet frame with the cusp edge of each leaflet extending along one ofthe cusp regions, and a commissure edge of each leaflet meeting acommissure edge of an adjacent leaflet at one of the commissure regions;and three cusp positioners integrally attached to the leaflet frame anddisposed circumferentially about the flow axis, at least a portion ofeach cusp positioner being located adjacent to a flexible leaflet andaxially positioned between the free edge and cusp edge of the flexibleleaflet, the three cusp positioners extending radially farther outwardlythan the three commissure regions and configured for engagement withnative leaflets of a heart valve; wherein the leaflet frame has a fabriccovering along substantially its entire length, the fabric coveringdefining a flange, wherein the arcuate cusp edges of the flexibleleaflets attach to the fabric covering flange; wherein the fabriccovering flange projects generally outwardly from the leaflet frame, andthe cusp edges of the flexible leaflets extend radially outwardly pastand underneath the leaflet frame, and are sewn to the fabric coveringflange.
 7. A collapsible prosthetic heart valve, comprising: acollapsible leaflet frame having an inflow end and an outflow end andthree cusp regions intermediate three commissure regions, the three cuspregions being positioned at the inflow end of the leaflet frame andcircumferentially about a flow axis defined within the support frame,the three commissure regions being positioned at the outflow end of theleaflet frame and circumferentially about the flow axis; three separate,flexible leaflets attached to the leaflet frame, each leaflet having anarcuate cusp edge opposite a free edge and a pair of commissure edgestherebetween, the leaflets being attached around the leaflet frame withthe cusp edge of each leaflet extending along one of the cusp regions,and a commissure edge of each leaflet meeting a commissure edge of anadjacent leaflet at one of the commissure regions; and three cusppositioners integrally attached to the leaflet frame and disposedcircumferentially about the flow axis, at least a portion of each cusppositioner being located adjacent to a flexible leaflet and axiallypositioned between the free edge and cusp edge of the flexible leaflet,the three cusp positioners extending radially farther outwardly than thethree commissure regions and configured for engagement with nativeleaflets of a heart valve; wherein each flexible leaflet has a pair oftabs extending on either side of its free edge, wherein two tabs ofadjacent flexible leaflets meet and pass together to the outside of theadjacent commissure region of the leaflet frame and are attached theretousing sutures through the tabs.
 8. A collapsible prosthetic heart valve,comprising: a continuous, collapsible leaflet frame shaped forimplantation within a defective native heart valve, the frame having aperiphery defined by only three U-shaped cusp regions intermediate threeU-shaped commissure regions, the three U-shaped cusp regions beingpositioned at an inflow end of the leaflet frame and circumferentiallyabout a flow axis defined within the leaflet frame, the three U-shapedcusp regions defining at least a portion of a terminal end of theleaflet frame, the three U-shaped commissure regions being positioned atan outflow end of the leaflet frame and circumferentially about the flowaxis; a cloth covering extending around the leaflet frame; and threeseparate, flexible leaflets attached to the leaflet frame, each leaflethaving an arcuate cusp edge opposite a free edge and a pair ofcommissure edges therebetween, the leaflets being attached around theleaflet frame with the cusp edge of each leaflet extending along one ofthe U-shaped cusp regions, and a commissure edge of each leaflet meetinga commissure edge of an adjacent leaflet at one of the U-shapedcommissure regions, the commissure edges of each leaflet furtherincluding a tab, wherein the tabs of two adjacent leaflets extendthrough the U-shaped commissure region, diverge on the outside ofU-shaped commissure region, and are attached to the leaflet frame on theoutside of the U-shaped commissure region.
 9. A collapsible prostheticheart valve, comprising: a continuous, collapsible leaflet frame havinga periphery defined by only three U-shaped cusp regions intermediatethree U-shaped commissure regions, the three U-shaped cusp regions beingpositioned at an inflow end of the leaflet frame and circumferentiallyabout a flow axis defined within the leaflet frame, the three U-shapedcusp regions defining at least a portion of a terminal end of theleaflet frame, the three U-shaped commissure regions being positioned atan outflow end of the leaflet frame and circumferentially about the flowaxis; a cloth covering extending around the leaflet frame; threeseparate, flexible leaflets attached to the leaflet frame, each leaflethaving an arcuate cusp edge opposite a free edge and a pair ofcommissure edges therebetween, the leaflets being attached around theleaflet frame with the cusp edge of each leaflet extending along one ofthe U-shaped cusp regions, and a commissure edge of each leaflet meetinga commissure edge of an adjacent leaflet at one of the U-shapedcommissure regions, the commissure edges of each leaflet furtherincluding a tab, wherein the tabs of two adjacent leaflets extendthrough the U-shaped commissure region, diverge on the outside ofU-shaped commissure region, and are attached to the leaflet frame on theoutside of the U-shaped commissure region; and three cusp positionersrigidly fixed with respect to the leaflet frame and disposedcircumferentially about the flow axis, each cusp positioner beinglocated at the outflow end of the support frame and intermediate two ofthe commissure regions of the leaflet frame, each cusp positioner havinga U-shape with an apex of the U-shape pointing toward the outflow end ofthe leaflet frame and two legs of the U-shape pointing toward the inflowend.
 10. The heart valve of claim 8, wherein the heart valve furtherincludes three cusp connectors rigidly fixed with respect to the leafletframe and disposed circumferentially about the flow axis, each cuspconnector being located at the inflow end of the leaflet frame andintermediate two of the cusp regions of the leaflet frame.
 11. The heartvalve of claim 10, wherein an inflow periphery of the heart valve isdefined along the alternating and rigidly fixed cusp regions and cuspconnectors.
 12. The heart valve of claim 8, wherein the leaflet framehas a fabric covering along substantially its entire length, the fabriccovering defining a flange, wherein the arcuate cusp edges of theflexible leaflets attach to the fabric covering flange.
 13. The heartvalve of claim 12, wherein the fabric covering flange projects generallyoutward from the leaflet frame, and the cusp edges of the flexibleleaflets extend radially outward past and underneath the leaflet frame,and are sewn to the fabric covering flange.